Anti-carcinogenic activity of simvastatin during the promotion phase of radiation-induced mammary tumorigenesis of rats.

Pregnant Wistar-MS rats received whole body irradiation with 2.6 Gy gamma-rays from a 60Co source at day 20 of pregnancy. Control rats were fed a basal diet and were implanted with a diethylstilbestrol (DES) pellet at 30 days after weaning. In the experimental group, rats were fed a diet containing simvastatin immediately after weaning and received a DES pellet at 30 days after weaning. A high incidence of total mammary tumours was observed in the rats fed the control diet and treated with DES for 1 year. The administration of dietary simvastatin together with DES treatment significantly decreased the incidence of mammary tumours. The development of adenocarcinoma in the control rats was significantly higher than that in the rats fed the simvastatin diet. After the administration of simvastatin to the experimental group for 1 year, the serum estradiol-17beta concentration in these rats was markedly reduced, but that of prolactin was not. No significant difference was seen in the development of the mammary glands between rats fed the control diet and those fed the simvastatin diet by whole mount observations. Simvastatin feeding produced an increased development of ER- PgR- tumours and a reduced incidence of ER+ PgR+ tumours. These findings suggest that simvastatin has a potent preventive activity during the DES-dependent promotion/progression phase of radiation-induced mammary tumorigenesis.